Biomedical subjects
Publications and source records attributed to R Griffiths.
This is the last in the Back to Basics series of articles--for now at least. I would like to thank all the authors for their pieces. I've learnt and relearnt from each of them. The completed set of articles will be available as one document in October, and will be launched at Congress--yet another reason to attend! Bye for now.
Accelerated infusions are potentially useful in the investigation of pharmacokinetic linearity. However, little information exists to validate this technique or to demonstrate its limitations. This investigation was performed to determine whether accelerated infusion regimens reliably estimate the range of pharmacokinetic linearity for molecules of varying pharmacokinetic properties, to evaluate the ability of accelerated infusions to identify pharmacokinetic nonlinearity, and to validate the accelerated infusion technique using compounds with known pharmacokinetic parameters. Simulations incorporating accelerated infusion as the input function resulted in the anticipated concentration-time profiles that contained an initial lag phase before reaching a linear slope. This lag phase increased with increasing distributional volume and in some instances was sufficiently great to obscure or prevent the linear portion of the profile. These simulations also revealed that clearance estimated from the apparently linear portion of the concentration-time profile can be erroneous under some conditions, as for large-volume compounds. Simulations of structured nonlinearity produced the predicted profiles for compounds with low to moderate volumes of distribution while demonstrating that modeling of data derived from compounds with large volumes of distribution may be inaccurate. Finally, experiments using accelerated infusions with various test compounds further demonstrated the usefulness of this technique while presenting limits imposed on the interpretation of the data. The results of this investigation indicate that the accelerated infusion may be used to determine pharmacokinetic linearity for compounds within certain pharmacokinetic boundaries, but that appropriate caution should be exercised in the extent of interpretation that should be extracted from such studies.
Sex ratio theory predicts that, if prevailing ecological or social circumstances differentially influence the fitness benefits of offspring of each sex, parents should adjust their production accordingly to maximize fitness. For species in which sex is chromosomally determined, such as birds and mammals, a differential effect of maternal condition on the fitness of male and female young is one important route whereby selection is expected to favor a bias in the offspring sex ratio at birth or egg laying. However, despite its central place in sex allocation theory, this hypothesis has rarely been tested in wild populations. We manipulated maternal condition upward and downward in a sexually dimorphic wild bird and examined the effect on offspring survival and on offspring sex ratio. The survival to fledging of male, but not female, young was substantially reduced if they came from less well provisioned eggs produced by females in relatively poor condition. As female condition, and thereby her capacity to produce high quality eggs, declined, she progressively skewed the sex ratio of her eggs toward females; i.e., she produced more of the sex with the higher survival prospects. The decline in the survival of male offspring, and the sex ratio bias, was removed when maternal condition was enhanced. These results provide experimental evidence of an adaptive, facultative adjustment of sex ratio in response to changes in maternal condition in wild birds.
The preference of female blue tits, Parus caeruleus, is correlated with the brightness of the ultraviolet (UV) crest; there is also assortative mating with respect to the crest's UV/violet chroma. However, manipulation of plumage reflectance is necessary to infer a direct causal link between UV plumage and mate choice. We gave both male and female blue tits a choice between a UV-reflecting ('UV+') partner and a partner whose UV plumage reflectance had been removed ('UV-'). Male blue tits significantly preferred UV+ females. Similarly, female blue tits tended to prefer UV-reflecting males, but their UV+ preferences were nonsignificant. Neither sex showed a preference when conspecifics were replaced by a heterospecific. This study suggests mutual mate choice but male choice may be more strongly influenced by the visual appearance of potential mates. This is one of a few studies to show male mate preferences and the first demonstration of a direct relationship between UV reflectance and male mate choice. Copyright 1999 The Association for the Study of Animal Behaviour.
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Sex identification is a problem in research and conservation. It can often be solved using a DNA test but this is only an option if a sex-specific marker is available. Such markers can be identified using the amplified fragment length polymorphism (AFLP) technique. This is usually a taxonomic method, as it produces a DNA fingerprint of 50-100 PCR bands. However, if male and female AFLP products are compared, sex-specific markers are confined to the heterogametic sex and can rapidly be identified. Once a marker is found, AFLP can be used to sex organisms directly or the marker can be sequenced and a standard PCR test designed.
BACKGROUND: Chronic renal allograft rejection is the leading cause of late graft failure. However, its pathogenesis has not been defined. METHODS: To explore the pathogenesis of chronic rejection, we studied a mouse model of kidney transplantation and examined the effects of altering the expression of donor major histocompatibility complex (MHC) antigens on the development of chronic rejection. RESULTS: We found that long-surviving mouse kidney allografts develop pathological abnormalities that resemble chronic rejection in humans. Furthermore, the absence of MHC class I or class II antigens did not prevent the loss of graft function nor alter the pathological characteristics of chronic rejection. Expression of transforming growth factor-beta (TGF-beta), a pleiotropic cytokine suggested to play a role in chronic rejection, was markedly enhanced in control allografts compared with isografts. However, TGF-beta up-regulation was significantly blunted in MHC-deficient grafts. Nonetheless, these differences in TGF-beta expression did not affect the character of chronic rejection, including intrarenal accumulation of collagens. CONCLUSIONS: Reduced expression of either class I or II direct allorecognition pathways is insufficient to prevent the development of chronic rejection, despite a reduction in the levels of TGF-beta expressed in the allograft. This suggests that the severity of chronic rejection is independent of the level of MHC disparity between donor and recipient and the level of TGF-beta expression within the allograft.
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The altered kinetics of steady-state c-fos mRNA production in cultured cerebellar granule cells under excitotoxic conditions was investigated in neurons subjected to depolarising stimuli, namely, high KCl and L-glutamate (Glu), in which Ca2+ influx occurs by differing routes. Increases in intracellular-free calcium levels ([Ca2+]i) stimulated by nontoxic or toxic levels of Glu were blocked by selective N-methyl-D-aspartate (NMDA) receptor antagonism; were blocked only partially by the L-type channel blocker, nifedipine; and were unaffected by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)/kainate receptor antagonists. Glu-induced cell death was prevented only by NMDA receptor blockade. Exposure of cells to nontoxic levels of Glu resulted in a transient increase in c-fos mRNA levels, whereas an excitotoxic dose produced a delay in the appearance of c-fos mRNA but a subsequent, progressive, and sustained (>4 hr) increase. An excitotoxic dose of Glu in combination with either nifedipine or selective NMDA receptor antagonists resulted in the normal, transient increase of c-fos mRNA levels. Chronic exposure to 55 mM KCl caused no cytotoxicity, although it resulted in a delayed, elevated increase in c-fos mRNA levels that was unaffected by NMDA receptor blockade but reverted to the normal, transient profile of c-fos mRNA formation when it was coadministered with nifedipine. The KCl-induced increase in [Ca2+]i levels was inhibited dramatically by nifedipine but was unaffected by any of the ionotropic Glu receptor antagonists. The results support the notion that the appearance of a delayed but elevated increase in steady-state c-fos mRNA levels following exposure to excitotoxic doses of Glu is mediated specifically by calcium influx via L-type voltage-gated channels.
OBJECTIVE: The present study was conducted to extend prior research on attention toward food and body weight and shape-related stimuli in women with eating disorders. METHOD: A modified Stroop color-naming task was completed by women with anorexia nervosa and by control females subdivided on a measure of dietary restraint. Eating disorder-relevant word categories included words connoting fatness, words connoting thinness, low caloric density food words, high caloric density food words, and neutral, control words. Valence effects were controlled for by including positively and negatively valenced emotion words. Stimuli were presented under both unmasked and masked conditions. RESULTS: Using unmasked stimuli, patients with anorexia nervosa, but not unrestrained or restrained eaters, had delayed color-naming latencies for both thin and fat word categories and, to a lesser extent, for high caloric density food words. No differences were observed with masked stimuli. DISCUSSION: Our findings suggest that both thinness and fatness are especially salient to women with anorexia. The lack of effects for emotion words suggests that these findings do not reflect a valence effect. We found no evidence for preconscious attentional biases in the masked condition.
OBJECTIVE: To investigate attentional biases for body shape and weight-related stimulus words among subjects with anorexia nervosa, bulimia nervosa, and control subjects classified using a measure of dietary restraint. METHODS: A visual probe detection task was used to assess attention toward stimulus words reflecting either a thin or a large physique and positively or negatively valenced emotion words. RESULTS: In comparison to controls, subjects with eating disorders detected target probes more slowly when they appeared in the same location as had stimulus words connoting a thin physique. In addition, there was a trend toward faster detection or target probes that appeared in the same location as had stimulus words connoting a large physique. Neither of these effects were observed among restrained eaters. DISCUSSION: Our results extend prior work suggesting information-processing biases for body shape and weight-related stimuli among persons with eating disorders.
OBJECTIVE: Few studies have investigated perceptions of operant conditioning programs by anorexic patients. This study examined patients' perceptions of the Bed Rest (BR) component which is employed in some operant conditioning programs. METHODS: A sample of 48 anorexic inpatients was administered a survey to elicit their attitudes towards BR. RESULTS: Results from the survey suggested that most patients perceived BR in a negative way. The main complaint, however, was not punishment or humiliation, as predicted, but isolation and boredom. A number of patients concluded that they wanted more individualization and distraction and less restriction while on BR. DISCUSSION: The findings justify the use of BR within a humane framework in the inpatient treatment of anorexia nervosa, but suggest that patients' perceptions of BR warrant systematic scrutiny.
A phylogeny for the lice (Insecta: Phthiraptera: genus Dennyus) parasitic on swiftlets (Aves: Collocalliinae) was constructed based on mitochondrial cytochrome b DNA sequences. This phylogeny is congruent with previous phenetic analyses of morphometric data for the lice. Comparison with a previously obtained phylogeny for the hosts indicates some degree of cospeciation. These cospeciation events are used to compare relative rates of evolution in the birds and their lice for the same segment of the cytochrome b gene. Cytochrome b is evolving two to three times more rapidly in lice than in birds, and louse cytochrome b is highly divergent compared to that of most other insects. Although generation time has been suggested as an explanation for the disparity in evolutionary rates between lice and their hosts, we suggest that the small effective population sizes of lice coupled with founder events occurring during transmission to new host individuals may be an important factor.
This report is of a case of a previously fit 65-year-old woman who developed postoperative liver dysfunction following an anaesthetic involving isoflurane. Biliary ultrasound demonstrated gallstones. However, serum antibodies to trifluoroacetylated proteins were detected, suggesting that immune sensitisation to the anaesthetic could have contributed to the impaired liver function.
Birds are difficult to sex. Nestlings rarely show sex-linked morphology and we estimate that adult females appear identical to males in over 50% of the world's bird species. This problem can hinder both evolutionary studies and human-assisted breeding of birds. DNA-based sex identification provides a solution. We describe a test based on two conserved CHD (chromo-helicase-DNA-binding) genes that are located on the avian sex chromosomes of all birds, with the possible exception of the ratites (ostriches, etc.; Struthioniformes). The CHD-W gene is located on the W chromosome; therefore it is unique to females. The other gene, CHD-Z, is found on the Z chromosome and therefore occurs in both sexes (female, ZW; male, ZZ). The test employs PCR with a single set of primers. It amplifies homologous sections of both genes and incorporates introns whose lengths usually differ. When examined on a gel there is a single CHD-Z band in males but females have a second, distinctive CHD-W band.
Tissue samples from 160 European hedgehogs, Erinaceus europaeus, representing eight small populations from a highly fragmented landscape in Oxfordshire, UK, were screened for polymorphism at six microsatellite loci. Permutation analysis of allelic compositions revealed no evidence for linkage disequilibrium among loci. Genotype proportions within populations and at five loci did not differ from those expected at Hardy-Weinberg equilibrium. However, significant heterozygote deficit and amplification failure of several samples necessitated removal of one locus from the analysis. Mean observed heterozygosity was 0.70. Average RhoST was 0.079 and differed significantly from zero, suggesting restricted gene flow among local populations. Pairwise Nm values and geographical distance were not correlated, indicating that factors other than distance affected dispersal.
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